Field of the Invention
The present invention relates to a novel method for preparing 3,5-bis(fluoroalkyl)pyrazole derivatives.
Description of Related Art
Polyfluoroalkylpyrazolylcarboxylic acid derivatives and 3,5-bis(fluoroalkyl)pyrazoles are important precursors of active fungicidal ingredients (cf. WO 2003/070705, WO 2008/013925, WO 2012/025557).
Monoperfluoroalkylpyrazolecarboxylic acid derivatives are typically prepared by reacting acylated acrylic acid derivatives with hydrazines (cf. WO 2009/112157 and WO 2009/106230). WO 2005/042468 discloses a method for preparing 2-dihaloacyl-3-aminoacrylic esters by reacting acid halides with dialkylaminoacrylic esters and subsequent cyclization thereof with alkyl hydrazines. WO 2008/022777 describes a method for preparing 3-dihalomethylpyrazole-4-carboxylic acid derivatives by reacting α,α-difluoroalkylamines in the presence of Lewis acids with acrylic acid derivatives and subsequent reaction thereof with alkyl hydrazines.
3,5-Bis(fluoroalkyl)pyrazoles are prepared by reacting bisperfluoroalkyldiketones (e.g. 1,1,1,5,5,5-hexafluoroacetylacetone) with hydrazines (cf. Pashkevich et al., Zhurnal Vsesoyuznogo Khimicheskogo Obshchestva named after D. I. Mendeleeva (1981), 26(1), 105-7), in which the yield is only 27-40%. The synthesis of bisperfluoroalkyldiketones by the Claisen reaction of fluoroalkylketones and esters of polyfluoroalkylcarboxylic acids is very complex. Polyfluoroalkylketones comprising a CH3 group (e.g. 1,1-difluoroacetone, 1,1,1-trifluoroacetone) react under strongly basic reaction conditions (NaH, KOtBu) not only with the ester, but in part with itself (aldol reaction), such that the yields are moderate. In addition, polyfluoroalkyldiketones are often volatile and highly toxic, such that isolation and purification thereof presents additional problems.
In the light of the prior art described above, it is an object of the present invention to provide a method that does not have the aforementioned disadvantages and hence provides a route to 3,5-bis(fluoroalkyl)pyrazole derivatives in high yields.